HUT58730A - Process for producing 3-amino-sidnonimine derivatives and pharmaceutical compositions containing them - Google Patents

Process for producing 3-amino-sidnonimine derivatives and pharmaceutical compositions containing them Download PDF

Info

Publication number: HUT58730A
Authority: HU; Hungary
Prior art keywords: formula; alkyl; group; optionally substituted; aryl
Prior art date: 1989-06-30

Application number

HU904037A

Other languages

English (en)

Hungarian (hu)

Other versions

HU904037D0 (en

Inventor

Eckard Kujath

Christian Baumgartner

Karl Schoenafinger

Malitta Just

Rudi Beyerle

Helmut Bohn

Joerg Ostrowski

Original Assignee

Cassella Farbwerke Mainkur Ag

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1989-06-30

Filing date

1990-06-29

Publication date

1992-03-30

1990-06-29 Application filed by Cassella Farbwerke Mainkur Ag filed Critical Cassella Farbwerke Mainkur Ag

1990-12-28 Publication of HU904037D0 publication Critical patent/HU904037D0/hu

1992-03-30 Publication of HUT58730A publication Critical patent/HUT58730A/hu

Links

238000000034 method Methods 0.000 title claims description 14
239000008194 pharmaceutical composition Substances 0.000 title claims description 10
150000001875 compounds Chemical class 0.000 claims description 77
239000002253 acid Substances 0.000 claims description 39
150000003839 salts Chemical class 0.000 claims description 33
239000003795 chemical substances by application Substances 0.000 claims description 27
125000000217 alkyl group Chemical group 0.000 claims description 24
239000002904 solvent Substances 0.000 claims description 15
239000004480 active ingredient Substances 0.000 claims description 14
125000003118 aryl group Chemical group 0.000 claims description 14
229910052757 nitrogen Inorganic materials 0.000 claims description 13
238000002360 preparation method Methods 0.000 claims description 11
238000005917 acylation reaction Methods 0.000 claims description 9
238000007363 ring formation reaction Methods 0.000 claims description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
125000000304 alkynyl group Chemical group 0.000 claims description 8
125000003710 aryl alkyl group Chemical group 0.000 claims description 8
125000004432 carbon atom Chemical group C* 0.000 claims description 8
239000002270 dispersing agent Substances 0.000 claims description 8
239000001257 hydrogen Substances 0.000 claims description 8
229910052739 hydrogen Inorganic materials 0.000 claims description 8
125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
230000010933 acylation Effects 0.000 claims description 7
125000001931 aliphatic group Chemical group 0.000 claims description 7
239000007864 aqueous solution Substances 0.000 claims description 7
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
125000003342 alkenyl group Chemical group 0.000 claims description 6
125000003545 alkoxy group Chemical group 0.000 claims description 6
125000000623 heterocyclic group Chemical group 0.000 claims description 6
125000003107 substituted aryl group Chemical group 0.000 claims description 6
150000002367 halogens Chemical class 0.000 claims description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
125000002883 imidazolyl group Chemical group 0.000 claims description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
125000000753 cycloalkyl group Chemical group 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
229910052736 halogen Inorganic materials 0.000 claims description 4
230000009935 nitrosation Effects 0.000 claims description 4
238000007034 nitrosation reaction Methods 0.000 claims description 4
125000004149 thio group Chemical group *S* 0.000 claims description 4
125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 3
SRANPMHVZAXTBA-UHFFFAOYSA-N n-(cyanomethyl)nitrous amide Chemical class O=NNCC#N SRANPMHVZAXTBA-UHFFFAOYSA-N 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 2
125000004076 pyridyl group Chemical group 0.000 claims description 2
125000001544 thienyl group Chemical group 0.000 claims description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
125000006828 (C2-C7) alkoxycarbonyl group Chemical group 0.000 claims 1
125000000041 C6-C10 aryl group Chemical group 0.000 claims 1
229940098465 tincture Drugs 0.000 claims 1
-1 methylene, ethylene, trimethylene, tetramethylene, methyl Chemical group 0.000 description 128
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 78
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
239000000203 mixture Substances 0.000 description 20
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 18
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
239000000243 solution Substances 0.000 description 13
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 10
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
238000001816 cooling Methods 0.000 description 9
238000009472 formulation Methods 0.000 description 9
239000011541 reaction mixture Substances 0.000 description 9
229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
235000017557 sodium bicarbonate Nutrition 0.000 description 9
235000010288 sodium nitrite Nutrition 0.000 description 9
239000000284 extract Substances 0.000 description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
238000000746 purification Methods 0.000 description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
239000004615 ingredient Substances 0.000 description 7
239000002244 precipitate Substances 0.000 description 7
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
229910052783 alkali metal Inorganic materials 0.000 description 6
239000002585 base Substances 0.000 description 6
239000000047 product Substances 0.000 description 6
238000003756 stirring Methods 0.000 description 6
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 5
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 5
239000002775 capsule Substances 0.000 description 5
150000001732 carboxylic acid derivatives Chemical group 0.000 description 5
239000003085 diluting agent Substances 0.000 description 5
230000000694 effects Effects 0.000 description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
239000000126 substance Substances 0.000 description 5
125000003944 tolyl group Chemical group 0.000 description 5
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
OWIKHYCFFJSOEH-UHFFFAOYSA-N Isocyanic acid Chemical compound N=C=O OWIKHYCFFJSOEH-UHFFFAOYSA-N 0.000 description 4
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
150000001241 acetals Chemical class 0.000 description 4
230000003213 activating effect Effects 0.000 description 4
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
238000006243 chemical reaction Methods 0.000 description 4
239000008298 dragée Substances 0.000 description 4
150000002148 esters Chemical class 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
239000007924 injection Substances 0.000 description 4
238000002347 injection Methods 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
239000000463 material Substances 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 4
229910017604 nitric acid Inorganic materials 0.000 description 4
239000003921 oil Substances 0.000 description 4
235000019198 oils Nutrition 0.000 description 4
150000007524 organic acids Chemical class 0.000 description 4
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 4
125000001424 substituent group Chemical group 0.000 description 4
239000003826 tablet Substances 0.000 description 4
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
229920002261 Corn starch Polymers 0.000 description 3
239000001828 Gelatine Substances 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
239000000460 chlorine Substances 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
230000008602 contraction Effects 0.000 description 3
239000008120 corn starch Substances 0.000 description 3
229940099112 cornstarch Drugs 0.000 description 3
239000000839 emulsion Substances 0.000 description 3
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
229920000159 gelatin Polymers 0.000 description 3
235000019322 gelatine Nutrition 0.000 description 3
229940093915 gynecological organic acid Drugs 0.000 description 3
230000002140 halogenating effect Effects 0.000 description 3
150000007522 mineralic acids Chemical class 0.000 description 3
230000000269 nucleophilic effect Effects 0.000 description 3
235000005985 organic acids Nutrition 0.000 description 3
229920005862 polyol Polymers 0.000 description 3
150000003077 polyols Chemical class 0.000 description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
239000000829 suppository Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
229940124597 therapeutic agent Drugs 0.000 description 3
HXVNBWAKAOHACI-UHFFFAOYSA-N 2,4-dimethyl-3-pentanone Chemical compound CC(C)C(=O)C(C)C HXVNBWAKAOHACI-UHFFFAOYSA-N 0.000 description 2
QQZOPKMRPOGIEB-UHFFFAOYSA-N 2-Oxohexane Chemical compound CCCCC(C)=O QQZOPKMRPOGIEB-UHFFFAOYSA-N 0.000 description 2
NZZOLLHLSZVJTJ-UHFFFAOYSA-N 2-[(2,6-dimethylpiperidin-1-yl)amino]-3-phenoxypropanenitrile Chemical compound CC1CCCC(C)N1NC(C#N)COC1=CC=CC=C1 NZZOLLHLSZVJTJ-UHFFFAOYSA-N 0.000 description 2
YIWUKEYIRIRTPP-UHFFFAOYSA-N 2-ethylhexan-1-ol Chemical compound CCCCC(CC)CO YIWUKEYIRIRTPP-UHFFFAOYSA-N 0.000 description 2
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 2
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
UAMDWTCVJDBESC-UHFFFAOYSA-N 3-phenylpropanethial Chemical compound S=CCCC1=CC=CC=C1 UAMDWTCVJDBESC-UHFFFAOYSA-N 0.000 description 2
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 description 2
YNTLHLHNKMCASH-UHFFFAOYSA-N 4-benzylsulfanyl-3-methyl-2-(morpholin-4-ylamino)butanenitrile Chemical compound C1COCCN1NC(C#N)C(C)CSCC1=CC=CC=C1 YNTLHLHNKMCASH-UHFFFAOYSA-N 0.000 description 2
HCFAJYNVAYBARA-UHFFFAOYSA-N 4-heptanone Chemical compound CCCC(=O)CCC HCFAJYNVAYBARA-UHFFFAOYSA-N 0.000 description 2
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical compound C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 2
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
150000001299 aldehydes Chemical class 0.000 description 2
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 2
150000008044 alkali metal hydroxides Chemical class 0.000 description 2
125000005083 alkoxyalkoxy group Chemical group 0.000 description 2
125000005196 alkyl carbonyloxy group Chemical group 0.000 description 2
125000004414 alkyl thio group Chemical group 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
125000005219 aminonitrile group Chemical group 0.000 description 2
239000002220 antihypertensive agent Substances 0.000 description 2
229940030600 antihypertensive agent Drugs 0.000 description 2
150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
125000004104 aryloxy group Chemical group 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
238000009835 boiling Methods 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
239000000969 carrier Substances 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
125000000068 chlorophenyl group Chemical group 0.000 description 2
JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
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IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 1
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IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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LCHWKMAWSZDQRD-UHFFFAOYSA-N silylformonitrile Chemical compound [SiH3]C#N LCHWKMAWSZDQRD-UHFFFAOYSA-N 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
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HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
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239000011975 tartaric acid Substances 0.000 description 1
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LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
125000006493 trifluoromethyl benzyl group Chemical group 0.000 description 1
UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
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239000008158 vegetable oil Substances 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/04—1,2,3-Oxadiazoles; Hydrogenated 1,2,3-oxadiazoles
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Heart & Thoracic Surgery (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Cardiology (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

HU904037A 1989-06-30 1990-06-29 Process for producing 3-amino-sidnonimine derivatives and pharmaceutical compositions containing them HUT58730A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE3921460A DE3921460A1 (de)	1989-06-30	1989-06-30	Substituierte 3-aminosydnonimine, verfahren zu ihrer herstellung und ihre verwendung

Publications (2)

Publication Number	Publication Date
HU904037D0 HU904037D0 (en)	1990-12-28
HUT58730A true HUT58730A (en)	1992-03-30

Family

ID=6383970

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HU904037A HUT58730A (en)	1989-06-30	1990-06-29	Process for producing 3-amino-sidnonimine derivatives and pharmaceutical compositions containing them

Country Status (9)

Country	Link
US (1)	US5079244A (de)
EP (1)	EP0406661A1 (de)
JP (1)	JPH03128367A (de)
KR (1)	KR910000675A (de)
CA (1)	CA2020216A1 (de)
DD (1)	DD297972A5 (de)
DE (1)	DE3921460A1 (de)
HU (1)	HUT58730A (de)
ZA (1)	ZA905099B (de)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE4025604A1 (de) *	1990-08-13	1992-02-20	Cassella Ag	3-dicyclohexylamino-sydnonimine, verfahren zu ihrer herstellung und ihre verwendung
DE4337335A1 (de) *	1993-11-02	1995-05-04	Cassella Ag	Verfahren zur Herstellung von Sydnoniminium-hydrogensulfaten
JP4784568B2 (ja)	2007-07-11	2011-10-05	船井電機株式会社	電気機器の電源コード引出し部構造

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE1695897C3 (de) *	1966-07-04	1979-02-15	Takeda Chemical Industries Ltd	N-Acyl-sydnonimine, deren Salze, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel
DE1670127A1 (de) *	1966-08-09	1970-12-03	Boehringer Sohn Ingelheim	Verfahren zur Herstellung neuer substituierter 3-Amino-sydnonimine
NL145762B (nl) *	1970-05-27	1975-05-15	Sandoz Ag	Werkwijze ter bereiding van een farmaceutisch preparaat met hypotensieve/antihypertensieve werking, alsmede gevormd preparaat.
CH560178A5 (de) *	1970-06-30	1975-03-27	Sandoz Ag
DE2930736A1 (de) *	1979-07-28	1981-02-12	Cassella Ag	Pharmakologisch wirksame, substituierte 3-amino-sydnonimine, verfahren zu ihrer herstellung und ihre verwendung
DE3526068A1 (de) *	1985-07-20	1987-01-22	Cassella Ag	Substituierte 3-amino-sydnonimine, verfahren zu ihrer herstellung, ihre verwendung und sie enthaltende pharmazeutische praeparate
DE3702083A1 (de) *	1987-01-24	1988-08-04	Cassella Ag	Allylmercaptoacetyl-sydnonimine, verfahren zu ihrer herstellung und ihre verwendung
DE3732174A1 (de) *	1987-09-24	1989-04-06	Cassella Ag	Substituierte 3-aminosydnonimine, verfahren zu ihrer herstellung und ihre verwendung
DE3800830A1 (de) *	1988-01-14	1989-07-27	Cassella Ag	Substituierte 3-sydnonimine, verfahren zu ihrer herstellung und ihre verwendung

1989
- 1989-06-30 DE DE3921460A patent/DE3921460A1/de not_active Withdrawn
1990
- 1990-06-07 US US07/534,152 patent/US5079244A/en not_active Expired - Fee Related
- 1990-06-25 EP EP90112031A patent/EP0406661A1/de not_active Withdrawn
- 1990-06-28 JP JP2168612A patent/JPH03128367A/ja active Pending
- 1990-06-29 HU HU904037A patent/HUT58730A/hu unknown
- 1990-06-29 KR KR1019900009703A patent/KR910000675A/ko not_active Withdrawn
- 1990-06-29 DD DD90342361A patent/DD297972A5/de not_active IP Right Cessation
- 1990-06-29 CA CA002020216A patent/CA2020216A1/en not_active Abandoned
- 1990-06-29 ZA ZA905099A patent/ZA905099B/xx unknown

Also Published As

Publication number	Publication date
JPH03128367A (ja)	1991-05-31
EP0406661A1 (de)	1991-01-09
HU904037D0 (en)	1990-12-28
DE3921460A1 (de)	1991-01-03
DD297972A5 (de)	1992-01-30
KR910000675A (ko)	1991-01-30
CA2020216A1 (en)	1990-12-31
US5079244A (en)	1992-01-07
ZA905099B (en)	1991-04-24

Legal Events

Date	Code	Title	Description
1994-06-28	DFA9	Temporary prot. cancelled due to abandonment

Publication	Publication Date	Title
US4436743A (en)	1984-03-13	3-[N-(Lower alkyl)-N-(tetrahydro-3-thienyl 5,5-dioxide)]sydnonimines
HU203331B (en)	1991-07-29	Process for producing allyl-mercapto-acetyl-sidnonimine derivatives and pharmaceutical compositions containing them
US5486531A (en)	1996-01-23	Hydroxymethylfurazancarboxylic acid derivatives
HUT58730A (en)	1992-03-30	Process for producing 3-amino-sidnonimine derivatives and pharmaceutical compositions containing them
HU207730B (en)	1993-05-28	Process for producing new substituted 3-amino-sidnonimine derivatives and pharmaceutical compositions containing them
HUT55389A (en)	1991-05-28	Process for producing substituted 3-amino-sidnonimine and pharmaceutical compositions containing them as active components
US5179206A (en)	1993-01-12	Substituted 3-aminosydnone imines
US4937244A (en)	1990-06-26	Substituted 3-aminosydnonimines, processes for their preparation and their use
Santilli et al.	1979	Synthesis of 3‐arylsulfonylmethyl‐1, 2, 4‐oxadiazole‐5‐carboxylic acid derivatives
HU201535B (en)	1990-11-28	Process for producing substituted 3-aminosydnone imines and pharmaceutical compositions comprising such compounds as active ingredient
HUT61757A (en)	1993-03-01	Process for producing 3-piperazinosydnone imine derivatives and pharmaceutical compositions comprising same
US5120732A (en)	1992-06-09	Substituted 3-aminosyndone imines, a process for their preparation and their use
HUT62275A (en)	1993-04-28	Process for producing 3-aminosydnone imine derivatives and pharmaceutical compositions comprising same
US5006540A (en)	1991-04-09	Substituted 3-aminosydnonimines, processes for their preparation and their use
HUT66154A (en)	1994-09-28	Phenyl-1,2,5-oxadiazole derivatives, pharmaceutical preparations containing them and process for producing them
HUT60481A (en)	1992-09-28	Process for producing 3-(dicyclohexylamino)-sydnone imine derivatives and pharmaceutical compositions comprising same
CZ278933B6 (en)	1994-09-14	Substituted 3-aminosydnonimines, process of their preparation and a pharmaceutical preparation containing thereof
US5221680A (en)	1993-06-22	Substituted 3-aminosydnonimines
HUT61756A (en)	1993-03-01	Process for producing 3-aminosydnone imine derivatives and pharmaceutical compositions comprising same
CA2042321A1 (en)	1991-11-14	Substituted 3-aminosydnone imines, processes for their preparation and their use
DE3939550A1 (de)	1991-06-06	Substituierte 3-aminosydnonimine, verfahren zu ihrer herstellung und ihre verwendung